The objective of this research is the elucidation of the mechanisms by which certain polypeptide hormones are synthesized, stored, and secreted by tumor cells of both pituitary and non-pituitary origin and of the structures of the hormones, hormone fragments, and hormone precursors. The hormones under consideration include ACTH, alpha-MSH, beta-MSH and beta-LPH. The approach to this study will include: a) Establishing and maintaining functional, hormone-secreting, cloned mouse and human tumor cell lines in moderately large volume tissue culture; b) Purification and characterization of tumor hormones, including biologic activity, immunological reactivity, and determination of primary chemical structure; c) Elucidation of the mechanisms by which glucocorticoids selectively inhibit ACTH synthesis, including identification of the specific nonhistone chromatin "acceptor" proteins and the defects in the mechanism in tumors causing ectopic ACTH syndrome; d) Investigation of the molecular events involved in tumor hormone synthesis: isolation of ACTH messenger RNA, and cell-free translation of this mRNA. BIBLIOGRAPHIC REFERENCES: Orth, D.N., K. Tanaka, and W.E. Nicholson. The melanotropins. In "Hormones in Human Blood: Detection and Assay," A.N. Antoniades, ed., Harvard University Press, Cambridge, Massachusetts, 1976, p. 423. Garroway, N.W., D.N. Orth, and R.W. Harrison. Binding of glucocorticoid receptors by isolated nuclei of glucocorticoid responsive and nonresponsive cultured cells. Endocrinology 98:1092, 1976.